# Circadian Regulation of In Vitro Differentiated Adipocytes

> **NIH NIH F31** · DARTMOUTH COLLEGE · 2024 · $45,446

## Abstract

ABSTRACT
 Metabolic dysregulation is the major preventable risk factor for leading causes of chronic
disease-related deaths. More specifically, chronic obesity is correlated with adipocyte hypertrophy
and hyperplasia, both of which may be circadianly regulated. All circadian clocks are cell-intrinsic,
and circadian oscillators that are tissue-specific control metabolic homeostasis by fine-tuning
nutrient utilization; adipose tissue responds to microenvironmental changes in a clock-dependent
manner. Thermogenic adipocytes can redirect energy away from ATP production during nutrient
excess by disrupting the electrochemical proton gradient, producing heat in a process called Non-
Shivering Thermogenesis (NST). Thermogenic adipocytes are sometimes capable of cell-
autonomously sensing ambient temperature and adopting a reversible thermogenic profile. The
circadian clock's importance in this thermogenic plasticity is not well understood, nor the cellular
decision to adopt this state. The objective of this work is to understand how circadian rhythms
affect adipocyte biology, especially thermogenic plasticity. To delineate the relationship between
the cellular circadian system and adipocyte biology in the absence of organismal cues, circadian
output will be characterized in Specific Aim 1 by transcriptionally profiling in vitro differentiated
adipocytes from inguinal adipose tissue over 3 circadian days with a 2-hour resolution via
RNAseq. In this way I will determine what aspects of adipocyte biology and environmental stimuli
can be influenced by time-of-day. Though multilocularity and mitochondrial abundance are not
indicators of thermogenic potential per se, these two organelles are intricately involved in NST.
To extend the hypothesis that thermogenic plasticity is clock-controlled, I will use quantitative
fluorescence live cell microscopy to characterize lipid droplet and mitochondrial spatial patterning
and thereby describe organelle morphology as a function of circadian time. In Specific Aim 2 I
will determine the cell-autonomous clock’s role in heat production, the quintessential component
of thermogenesis, using infrared thermal imaging to identify rhythms in heat production (1) during
a state of decreased bioenergetic efficiency via uncoupling with BAM15 and (2) by suppressing
UCP1 with purine nucleotides. The long-term goal of this proposal is to determine the clock’s role
in regulating thermogenesis. Findings from this study will increase our understanding of clock-
controlled energy metabolism and adipocyte dysfunction, advancing our understanding of the
non-linear association between weight, energy expenditure and risk in chronic disease.

## Key facts

- **NIH application ID:** 10652393
- **Project number:** 5F31DK131890-02
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Armina-Lyn M Frederick
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $45,446
- **Award type:** 5
- **Project period:** 2022-07-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10652393

## Citation

> US National Institutes of Health, RePORTER application 10652393, Circadian Regulation of In Vitro Differentiated Adipocytes (5F31DK131890-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10652393. Licensed CC0.

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